Diet, weight, and metabolism are intricately linked, so learning their relationship is not any simple activity. Individuals’s consuming habits embody all kinds of meals, lots of that are shared between various kinds of diets; this complexity makes it tough to ascertain trigger and impact. “What must you eat? What must you not eat?” mused Jonathan Lengthy, a biochemist at Stanford College. To sort out this problem, Lengthy focuses on isolating single, chemically well-defined parts of diets to raised perceive their affect on the physique.
Taurine, an amino acid generally present in meats, shellfish, and vitality drinks, is a daily a part of many diets. Whereas people naturally produce taurine, dietary taurine can assist the immune system and enhance cardiovascular well being. It’s usually used as a complement for weight reduction or to boost train efficiency. Given taurine’s involvement in varied physiological capabilities, researchers have been eager to know how it’s metabolized within the physique, as it’s transformed into completely different taurine-containing molecules. This prompted Lengthy to discover its metabolic pathways and he homed in on an understudied taurine metabolite referred to as N-acetyltaurine.1
Jonathan Lengthy is concerned with mammalian metabolism, taking a extra chemical lens in the direction of learning vitality steadiness and weight problems.
Jonathan Lengthy
N-acetyltaurine, fashioned when taurine binds to acetate throughout taurine degradation, can fluctuate in response to food plan and train. Nevertheless, the main points of its breakdown course of and potential capabilities stay unclear. The researchers have been notably concerned with how this molecule may relate to points corresponding to vitality steadiness or weight problems. Whereas investigating this hole, the researchers recognized an enzyme answerable for breaking down N-acetyltaurine and linked this pathway to physique weight regulation. Their findings, revealed in Nature, revealed that mice missing this enzyme accrued excessive ranges of N-acetyltaurine and when fed a high-fat food plan, resisted diet-induced weight problems.2 The work suggests the taurine metabolism pathway might assist regulate physique weight and meals consumption, highlighting its potential as a goal for growing new weight-loss medicine just like Ozempic.
Lengthy’s fascination with metabolism stems from its function in how the physique processes meals and converts it into vitality—a course of that impacts well being, getting older, and weight. In exploring metabolites, he got here throughout taurine, a surprisingly considerable but understudied compound present in meals like shellfish, meat, and vitality drinks. The shortage of analysis on taurine intrigued him.
He remarked, “It’s form of fascinating and strange for one thing [like taurine] that’s so considerable and prevalent within the meals we eat, however there’s really little or no understood about how that impacts our our bodies.” To higher perceive the connection between food plan and its potential results on weight, he tackled the query from a chemical perspective.
To do that, the researchers used an old-school biochemistry strategy to seek out the enzyme, or enzymes, answerable for regulating N-acetyltaurine. “We didn’t know the place it could be,” defined Lengthy. They floor up and purified enzymatic merchandise from completely different mouse organs, on the lookout for merchandise of N-acetyltaurine degradation: acetate and taurine. Then, the researchers used chromatography to separate the enzymatic merchandise and seek for spikes in hydrolysis exercise, which helped them establish three enzyme candidates. Of those candidates, the researchers discovered that an orphan enzyme referred to as phosphotriesterase-related (PTER) was vital for N-acetyltaurine hydrolysis.
A earlier large-scale genetic research had steered that the PTER gene was linked to physique weight in individuals, however nearly nothing was identified in regards to the enzyme itself.3 This spurred Lengthy to determine the connection between the 2.
To research the physiological relevance of PTER, the researchers used a Pter knockout (KO) mouse mannequin. Throughout all tissues, mice with out PTER developed N-acetyltaurine ranges that Lengthy described as, “via the roof” in comparison with wild kind animals. Lengthy questioned how this attribute would have an effect on physique weight regulation in mice on a high-fat food plan.
Whereas people eat various quantities of taurine of their diets, normal mouse chow sometimes lacks taurine. Since taurine is a part of PTER exercise, the researchers added it to the ingesting water of Pter KO and wild kind mice whereas feeding them a high-fat food plan. After eight weeks, Pter KO mice ate much less and resisted diet-induced weight problems. These mice additionally confirmed improved glucose tolerance and insulin sensitivity in comparison with wild kind mice, doubtless as a consequence of this leanness. Nevertheless, Pter KO mice fed normal chow confirmed no modifications in weight or meals consumption, no matter taurine supplementation. These findings, Lengthy remarked, assist a gene-environment interplay, during which the Pter gene interacts with dietary taurine and the connection with physique weight turns into obvious within the presence of an environmental stimulus, corresponding to a high-fat food plan.
Chi Chen, a dietary biochemist on the College of Minnesota who characterised N-acetyltaurine a decade in the past as a biomarker for ethanol metabolism, remarked that he was glad to see different teams demonstrating the significance of this compound. He commented that this work has an fascinating angle to be translated into pharmacological purposes. “One factor that’s engaging is [that] that is an endogenous compound, so in a approach, you can take into account it as protected and never fear as a lot about unintended effects.”
Lengthy echoed the concept of leveraging these findings for therapies in physique weight regulation and added, “The truth that this Pter gene is said to physique weight management, not less than within the mouse, might result in the event of PTER inhibitors that concentrate on this pathway and complement weight reduction medicine like Ozempic.”
